Enantioselective Synthesis of 1,12-Disubstituted [4]Helicenes

Abstract

A highly enantioselective synthesis of 1,12-disubstituted [4]carbohelicenes is reported. The key step for the developed synthetic route is a Au-catalyzed intramolecular alkyne hydroarylation, which is achieved with good to excellent regio- and enantioselectivity by employing TADDOL-derived (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol) α-cationic phosphonites as ancillary ligands. Moreover, an appropriate design of the substrate makes the assembly of [4]helicenes of different substitution patterns possible, thus demonstrating the synthetic utility of the method. The absolute stereochemistry of the newly prepared structures was determined by X-ray crystallography and characterization of their photophysical properties is also reported.

Keywords: Au catalysis; [4]helicenes; asymmetric catalysis; enantioselective synthesis; ligand design.

Figure 1

Inversion barriers for [4]‐, [5]‐, and [6]helicenes and their Me‐substituted derivatives; [a] Calculated values at the B3LYP/6‐31G(d) level of theory; [b] Experimental values.

Figure 2

Synthetic approaches to the enantioselective synthesis of 1,12‐disubstituted [4]helicenes.

Scheme 1

Synthesis of [4]helicene precursors and structures of the catalysts tested. Reagents and conditions: a) Pd₂(dba)₃ (5 mol %), SPhos (10 mol %), Cs₂CO₃ (4 equiv), THF/H₂O (10:1), 80 °C, 24 h, 3 a, 62 %; 3 b, 67 %; 3 c, 65 %; 3 d, 89 %; b) 19 (9 mol %), AgSbF₆ (9 mol %), DCM, 7 a, 87 %; 7 b, 42 %, both from 6 (two steps); c) Tf₂O (1.5 equiv), pyridine (4.0 equiv), and then 5 a or 5 c, Pd₂(dba)₃ (5 mol %), SPhos (10 mol %), Cs₂CO₃ (2 equiv), THF/H₂O (10:1), 80 °C, 24 h, 8 a, 60 %; 8 b, 25 % (two steps). X‐ray structure of 2 g, H atoms, co‐crystallized solvents and SbF₆ anions are removed for clarity. Arene moieties are drawn as reduced sticks, ellipsoids drawn at 50 % probability level.16

Scheme 2

Synthesis of non‐symmetric [4]helicene precursors. Reagents and conditions: a) Pd(AcO)₂ (3 mol %), SPhos, (3 mol %), K₃PO₄ (2.0 equiv), toluene/dioxane (10:1), 12 a, 92 %, 12 b, 91 %, 12 c, 87 %; b) Ohira–Bestmann reagent (3.0 equiv), K₂CO₃ (3.0 equiv), MeOH, 13 a, 95 %, 13 b, 99 %, 13 c, 87 %; c) PhI (1.0 equiv), CuI (3 mol %), PdCl₂(PPh₃)₂ (2 mol %), Et₃N (5 mL), 14 c, 89 %, 14 d, 71 %; d) PtCl₂ (10 mol %), toluene, 85 °C, 15 a, 60 %; 15 b, 89 %; e) 19 (10 mol %), AgSbF₆ (10 mol %), DCM, 15 c, 73 %; 15 d, not isolated; f) BBr₃, DCM, 16 a, 99 %; 16 b, 85 %; 16 c, 73 %; g) BCl₃ (2 equiv), C₆HMe₅ (3 equiv),16 d, 67 % (two steps); h) Tf₂O (1.2 equiv), Et₃N, 17 a, 79 %; 17 b, 75 %; 17 c, 98 %, 17 d, 95 %; i) 5 a–c, Pd₂(dba)₃ (5 mol %), SPhos (10 mol %), Cs₂CO₃ (2 equiv), THF/H₂O (10:1), 80 °C, 24 h, 18 a, 89 %; 18 b, 92 %; 18 c, 68 %; 18 d, 51 %; 18 e, 43 %; 18 f, 38 %; 18 g, 67 %; 18 h, 75 %; 18 i, 62 %; 18 j, 81 %.

Figure 3

X‐ray structure of rac‐1 a (left) and 20 j (right). H atoms are removed for clarity and ellipsoids drawn at 50 % probability level.16

Figure 4

Circular dichroism spectra of 1 a–e in dichloromethane.